This is a continuation of our efforts to determine the role of genetic factors in predicting resistance and susceptibility to coronary artery disease (CAD). We will utilize assays of candidate genes and their products that have been recently developed to characterize an individual's genotype. These assays will provide measurements of the LDL receptor function, qualitative and quantitative phenotypes of seven apolipoproteins and restriction fragment length polymorphisms for the candidate genes that code for these apolipoproteins. We will utilize the biochemical and clinical measurements of hyperlipidemia and CAD to characterize the cardiovascular health of each individual. The proposed studies will combine information about the genotype, gene products, intermediate phenotypes of lipid metabolism, and the CAD endpoint to establish the genetic factors that can be used to predict CAD. We expect that a fraction of the information about an individuals risk to CAD provided by DNA and gene product polymorphisms will be expressed through the intermediate phenotypes of lipid metabolism and a fraction will act independently in a pleiotropic fashion to predict CAD. In Aim 1 we will collect 300 three-generation families selected to represent the Rochester, Minnesota population. We require these additional date on families to obtain adequate numbers of individuals at risk to establish which of the measurements of the genetic loci and intermediate phenotypes of lipid metabolism predict risk of CAD. In Aim 2 we will determine which genotypes and phenotypes characterized in Aim 1 can be used to discriminate between seven different clinical types of CAD. In Aim 3 we will determine whether or not any of the genotypes and/or phenotypes identified in Aim 1 can be used to predict the response of hyperlipidemia to drug therapy.